This invention relates to methods and apparatus for tracking disease progression using magnetic resonance imaging, including methods and apparatus for efficiently and precisely tracking the progression of rheumatic diseases affecting cartilage.
Osteoarthritis is a prevalent disease characterized mainly by cartilage degradation that is clinically reflected by a gradual development of joint pain, stiffness, and loss of motion. Osteoarthritis is extremely frequent in the general population, and it is estimated that its radiological prevalence is close to 50% overall. This figure is even higher in the elderly, with as much as 75% of the population between ages of 55 and 64 exhibiting some degree of radiological osteoarthritis in one or more joints. Although this disease is often benign, severe degenerative changes may cause serious disability.
Clinical osteoarthritis is now understood to be a complex interaction of degradation and repair of the cartilage, bone, and synovium, with secondary components of inflammation. The biochemical changes of osteoarthritis affect several cartilage components, including major matrix constituents, proteoglycans, and collagens. Decreased proteoglycan content in conjunction with damaged collagen structure leads to functional loss of normal matrix physiologic properties. Although the etiology of osteoarthritis is multiple and includes mechanical and biochemical factors, it appears that these culminate in an increased synthesis of proteolytic enzymes by the chondrocytes, which in turn leads to cartilage destruction.
There is no known cure for osteoarthritis, and current treatments are essentially limited to reliving the patient""s symptoms. Research is under way, however, to find a therapeutic agent that will slow or stop the progression of the disease. One current approach to developing pharmacological treatments for osteoarthritis focuses on subchondral bone sclerosis, which is a well-recognized manifestation of osteoarthritis that could play a major role in the onset and/or progression of the disease.
Unfortunately, evaluating the efficacy of such agents is not an easy, straightforward process. For many years, studies of drug interventions on symptomatic knee osteoarthritis focused only on clinical parameters like pain and joint function, without assessing the anatomical impact of the disease (i.e., cartilage degradation and bone sclerosis). Simple radiographs are now often used in clinical trials for osteoarthritis to establish inclusion criteria, but such trials have not employed them to assess disease progression. More complex radiographic methods have also been proposed for measuring joint space width, such as the Buckland-Wight method, which may be used in clinical trials. Arthroscopy appears reliable and sensitive to changes, but it only allows for evaluation of the cartilage surface. It also appears to be somewhat subjective even when independently trained evaluators review video recordings of the procedures, and, above all, it is invasive.
A number of academic researchers have evaluated the use of Magnetic Resonance Imaging (MRI) for orthopedic investigations over the last ten years. Some researchers have proposed using MRI to reproducibly quantify articular dimensions to follow disease progression, and thereby assess whether proposed treatments may be responsible for changing the rate of cartilage loss. But the actual application of these proposed systems to the complex problem of making meaningful measurements on acutal diseased joints has not been shown to be entirely successful. This may be due to one or more of a variety of shortcomings, including extensive manual treatment and interpretation of data, excessive reliance on subjective human judgment, insufficient accuracy or repeatability to achieve meaningful results when used on actual diseased joints, inability to distinguish secondary symptoms, and/or excessively long scan times.
Several aspects of the invention are presented in this application. These relate to methods and apparatus for tracking disease progression using magnetic resonance
In one general aspect, the invention features an orthopedic magnetic resonance imaging system that includes a source of magnetic resonance imaging data sets 250 resulting from successive magnetic resonance imaging acquisitions from a diseased joint of a patient. A segmentation module is responsive to the source of magnetic resonance imaging data sets and operative to segment surfaces in the joint based on information contained within at least one of the data sets. A registration module 252 is responsive to the source of magnetic resonance imaging data sets and operative to spatially register, in three dimensions, information represented by a first of the data sets with respect to information represented by one or more further data sets for the same patient. A comparison module 254 is responsive to the registration module and operative to detect differences between information represented by the data sets caused by progression of the disease in the joint of the patient between acquisitions.
In preferred embodiments, the comparison module can be operative to detect changes in cartilage thickness within the joint. The comparison module can be operative to detect changes in cartilage volume within the joint. The comparison module can be operative to detect changes in characteristics of cartilage material within the joint, which can be reflected in changes in magnetic resonance signal from the cartilage material. The system can further include a cross-patient comparison module 256 responsive to the comparison module to compare detected differences for the patient with detected differences for at least one other patient. The system can further include a multi-patient database with the cross-patient comparison module including a statistical analysis module operative to derive statistical information about the progression of disease in the joints of a number of patients. The registration module can be operative to spatially register the data sets to within an average RMS value of about 50 microns, or even 10 microns. The registration module can include an automatic registration module operative to perform at least a three-dimensional preliminary spatial registration independent of user input. The registration module can be operative to perform the registration based on previously acquired magnetic resonance imaging data for the same patient. The segmentation module can be an automatic segmentation module responsive to the source of magnetic resonance imaging data sets and operative to automatically segment anatomical features in the patient with substantially only supervisory and artifact-correcting user input. The source of magnetic resonance imaging data can be operative to provide data sets optimized for the detection of at least bone and cartilage. The source of magnetic resonance imaging data can include a magnetic resonance imaging system operative to acquire the data sets using a sequence is less than about 30 minutes in duration. The source of magnetic resonance imaging data sets can include a magnetic resonance imaging system and a support assembly operative to immobilize the diseased joint within the magnetic resonance imaging system with the joint at a predetermined three-dimensional position. The magnetic resonance imaging system can include a knee coil with the support assembly including a heel constraint and at least two flexible wedges that are each operative to interact with a leg of the patient and the knee coil. The support assembly can be operative to repeatedly immobilize the joint at predetermined three-dimensional positions that fall within a range of less than 17 or even 7 millimeters along the longitudinal axis of the magnetic resonance imaging system. The system can further include a differential display module operative to generate a difference map depicting differences between the data sets detected by the comparison module. The joint can be a load-bearing joint, with the imaging data sets include imaging data for at least the majority of the load bearing surfaces of the joint. The segmentation module can employ an active contour algorithm. The active contour algorithm can be a subpixel active contour algorithm. The segmentation module can employ an active contour algorithm configured to segment open contours with minimal operator intervention. The segmentation module can employ a three-dimensional gradient-driven active contour algorithm. The comparison module can be operative to detect differences between information represented by the data sets within one or more sub-regions of a surface of the joint caused by progression of the disease in the joint of the patient between acquisitions. The sub-regions can be based on polar coordinates or Cartesian coordinates.
In another general aspect, the invention features a method of monitoring disease progression in a joint that includes obtaining successive images of a same joint for each of a plurality of patient, where at least some of the joints are diseased. The method also includes the steps of segmenting joint surfaces within at least one of the images each patient, and, for each of the patients, spatially registering joint features for one of the successive images with another of the successive images. Differences are detected between the registered successive images for each of the individual patients, and the differences are compared for different ones of the patients.
In preferred embodiments, the method can further include the step of administering a therapeutic agent to at least some of the patients before the acquisition of at least some of the successive images, and evaluating the differences between the registered successive images to obtain a measure of the efficacy of the therapeutic agent. The method can further include the step of evaluating the differences between the registered successive images to determine how to treat individual ones of the patients. The therapeutic agent can be designed to treat rheumatic diseases affecting the cartilage. The step of obtaining can include performing a magnetic resonance imaging acquisition and can further include the step of immobilizing the diseased joint with the joint at a predetermined flexion angle during the step of performing a magnetic resonance imaging acquisition. The step of obtaining can include performing a magnetic resonance imaging acquisition and further include the step of completely immobilizing the diseased joint with the joint at a predetermined three-dimensional position during the step of performing a magnetic resonance imaging acquisition. The step of immobilizing can be operative to repeatedly immobilize the joint at predetermined three-dimensional positions that fall within a range of less than 17 or even 7 millimeters along the longitudinal axis of the magnetic resonance imaging system used to perform the magnetic resonance imaging acquisition. The step of obtaining can include performing a magnetic resonance imaging acquisition, a step of positioning one or more markers proximate the joint during the magnetic resonance imaging, and a step of evaluating image distortion for the joint based on acquired image data for the markers. The step of obtaining can include performing a magnetic resonance imaging acquisition, a step of positioning one or more markers proximate the joint during the magnetic resonance imaging, and further including a step of evaluating patient movement artifact for the joint based on acquired image data for the marker. The step of positioning can position a pair of cylinders in orthogonal locations proximate the joint. The steps of detecting differences and comparing the differences can be operative to detect differences between information represented by the data sets within one or more sub-regions of a surface of the joint. The sub-regions can be based on polar coordinates or Cartesian coordinates.
In a further general aspect, the invention features an orthopedic magnetic resonance imaging system that includes means for obtaining successive images of a same joint for each of a plurality of patients, wherein at least some of the joints are diseased. Also included are means for segmenting joint surfaces within at least one of the images for each patient, means for spatially registering joint features for one of the successive images with another of the successive images for each of the patients, means for detecting differences between the registered successive images for each of the individual patients, and means for comparing the differences obtained for different ones of the patients.
In another general aspect, the invention features an orthopedic magnetic resonance imaging system that includes a source of magnetic resonance imaging data resulting from magnetic resonance imaging acquisitions from a diseased joint of a patient. The system also includes a segmentation module that is responsive to the source of magnetic resonance imaging data and to segmentation result storage, and that is operative to detect a boundary between two anatomical features of the joint in three dimensions based on both three-dimensional information from the diseased joint of the patient and prior segmentation results stored in the segmentation result storage.
In preferred embodiments, the system can further include a registration module responsive to the source of magnetic resonance imaging data and operative to spatially register three-dimensional image data from a first acquisition for the patient and three-dimensional image data from a later acquisition for the same patient.
In a further general aspect, the invention features a method of monitoring disease progression in a joint that includes obtaining a first magnetic resonance imaging data set resulting from magnetic resonance imaging acquisition of a joint of a patient, segmenting a boundary between two anatomical features of the joint based on the first magnetic resonance imaging data set, and saving segmentation information derived during the step of segmenting. A second magnetic resonance imaging data set resulting from a magnetic resonance imaging acquisition of the same joint for the same patient is then obtained, and the boundary between the same two anatomical features of the same joint of the same patient is segmented based on both the second magnetic resonance imaging data set and the segmentation information saved in the step of saving.
In preferred embodiments, the method can further include the step of administering a therapeutic agent for the disease to a plurality of patients, with the steps of obtaining, the steps of segmenting, and the step of saving being performed for a plurality of patients, and the method can further include the step of evaluating the effect of the therapeutic on the disease based on results of the steps of obtaining, the steps of segmenting, and the step of saving.
In another general aspect, the invention features an orthopedic magnetic resonance imaging system that includes means for obtaining a first magnetic resonance imaging data set resulting from magnetic resonance imaging acquisition of a joint of a patient and for obtaining a second magnetic resonance imaging data set resulting from a magnetic resonance imaging acquisition of the same joint for the same patient. Also included are means for segmenting a boundary between two anatomical features of the joint based on the first magnetic resonance imaging data set, means for saving segmentation information derived by the means for segmenting, and means for segmenting the boundary between the same two anatomical features of the same joint of the same patient based on both the second magnetic resonance imaging data set and the segmentation information saved by the means for saving.
In a further general aspect, the invention features an orthopedic magnetic resonance imaging system that includes a source of magnetic resonance imaging data resulting from magnetic resonance imaging acquisitions from a diseased joint of a patient, and a segmentation module that is responsive to the source of magnetic resonance imaging data sets and is operative to detect a boundary between two anatomical features of the joint in three dimensions by detecting an outline in each of a plurality of at least generally parallel planes within the volume, wherein the outline in at least some of the planes is based on data from at least one other of the planes.
In another general aspect, the invention features a method of monitoring disease progression in a joint that includes obtaining a first magnetic resonance imaging data set resulting from magnetic resonance imaging acquisition of a joint of a patient, and segmenting an outline of a boundary between two anatomical features of the joint of the patient in three dimensions by detecting an outline in each of a plurality of at least generally parallel planes within the volume, wherein the outline in at least some of the planes is based on data from at least one other of the planes.
In a further general aspect, the invention features an orthopedic magnetic resonance imaging system that includes means for obtaining a first magnetic resonance imaging data set resulting from magnetic resonance imaging acquisition of a joint of a patient, and means for segmenting an outline of a boundary between two anatomical features of the joint of the patient in three dimensions by detecting an outline in each of a plurality of at least generally parallel planes within the volume, wherein the outline in at least some of the planes is based on data from at least one other of the planes.
In another general aspect, the invention features a magnetic resonance imaging system that includes a source of magnetic resonance imaging data resulting from magnetic resonance imaging acquisition from an imaging volume for a patient, a fitting module operative to fit a biparametric surface to an anatomical feature described by the data for the patient, and a projection module responsive to the magnetic resonance imaging data source and operative to project at least a portion of the data representing the three-dimensional anatomical feature onto the biparametric surface.
In preferred embodiments, the surface can be a biparametric surface having a three-dimensional topology. The system can further include a display module responsive to the projection module to display the two dimensional surface on a planar display. The anatomical feature can include at least the condyles of the femur with the surface being a cylinder. The anatomical feature can include at least the plateau regions of the tibia and wherein the surface is a plane. The anatomical feature can include at least the posterior surface of the patella and wherein the surface is a cylinder. The system can further include means for performing image manipulations on data representing the two dimensional surface. The system can further include a repositioning module operative to user input to project the three-dimensional anatomical feature onto a further biparametric surface layers proximate the biparametric surface. The system can further include an inter-patient comparison module responsive to the projection module to compare results derived from the projections from the projection module for a plurality of different patients. The system can further include a display module responsive to the inter-patient comparison module to display comparison information for the projections.
In a further general aspect, the invention features a magnetic resonance imaging method that includes obtaining a magnetic resonance imaging data set resulting from a magnetic resonance imaging acquisition from an imaging volume for a patient, fitting a biparametric surface to an anatomical feature described by the data set for the patient, and projecting at least a portion of the data representing the three-dimensional anatomical feature onto the biparametric surface.
In preferred embodiments, the method can further include repeating the steps of obtaining, fitting, and projecting for a plurality of different patients, and can further include the steps of comparing resulting projections for the plurality of different patients.
In another general aspect, the invention features a magnetic resonance imaging system that includes means for obtaining a magnetic resonance imaging data set resulting from a magnetic resonance imaging acquisition from an imaging volume for a patient, means for fitting a biparametric surface to an anatomical feature described by the data set for the patient, and means for projecting at least a portion of the data representing the three-dimensional anatomical feature onto the biparametric surface.
In a further general aspect, the invention features a phantom for a magnetic resonance imaging system that includes a body defining a first cavity for holding a first material that has at least one magnetic resonance property that is substantially similar to that of cartilage, and a second cavity for holding a second material that has at least one magnetic resonance property that is substantially similar to that of an anatomical feature that is adjacent to cartilage.
In preferred embodiments, the cavities can be on the order of the thickness of joint features to be imaged using magnetic resonance imaging. The cavities can be on the order of 0.125 inches thick. The body can define a first partition separating the first and second cavities. The partition can be on the order of less than 100 microns thick. The body can further define a third cavity for holding a third material, with the body including a second partition separating the second and third cavities.
In another general aspect, the invention features a magnetic resonance imaging method that includes obtaining and processing a magnetic resonance image of a phantom of known geometry that simulates the contrast level between cartilage and at least one anatomical feature adjacent to cartilage, obtaining a magnetic resonance image of a joint of a patient, and processing results of the step of obtaining a magnetic resonance image of a joint of a patient based on results of the step of obtaining and processing a magnetic resonance image of a phantom.
In preferred embodiments, the step of processing can be a step of verifying that results of the step of obtaining a magnetic resonance image of a joint of a patient fall within a predetermined contrast range based on results of the step of obtaining a magnetic resonance image of a phantom. The step of processing can be a step of correcting results of the step of obtaining a magnetic resonance image of a joint based on results of the step of obtaining an image of a phantom. The step of obtaining a magnetic resonance image of a phantom and the step of obtaining a magnetic resonance image of a joint can be performed using a first magnetic resonance imaging configuration, and the method can further include a further step of obtaining a magnetic resonance image of a phantom of known geometry that simulates the contrast level between cartilage and at least one adjacent anatomical feature and a further step of obtaining a magnetic resonance image of a joint of a patient. The step of obtaining a magnetic resonance image of a phantom can be performed for a first material that has at least one magnetic resonance property that is substantially similar to that of bone and a second material that has at least one magnetic resonance property that is substantially similar to that of cartilage. The step of obtaining a magnetic resonance image of a phantom can be performed for a phantom that includes volumes on the order of the volumes of joint features to be imaged using magnetic resonance imaging.
In a further general aspect, the invention features a phantom for a magnetic resonance imaging system that includes first means having at least one magnetic resonance property that is substantially similar to that of cartilage, and second means having at least one magnetic resonance property that is substantially similar to that of an anatomical feature that is adjacent to cartilage.
In another general aspect, the invention features a magnetic resonance imaging system that includes a source of three-dimensional magnetic resonance imaging data sets resulting from magnetic resonance imaging acquisition from a joint of a patient, a segmentation module that is responsive to the source of magnetic resonance imaging data sets and is operative to detect a boundary between two anatomical features of the joint in three dimensions based on three-dimensional information from a first of the data sets, and a comparison module responsive to the segmentation module and to a second of the data sets and operative to compare boundary surface data resulting from segmentation by the segmentation module for the first data set with volumetric data from the second data set.
In preferred embodiments, the comparison module can be included in a second segmentation module operative to segment the same boundary between the same anatomical features in the second data set. The comparison module can be included in a registration module operative to spatially register the boundary between the anatomical features segmented in the first data set with the second data set.
In a further general aspect, the invention features a magnetic resonance imaging method that includes obtaining a first three-dimensional magnetic resonance imaging data set resulting from magnetic resonance imaging acquisition from a joint of a patient, segmenting a boundary between two anatomical features of the joint of the patient based on the first magnetic resonance imaging data set, obtaining a second three-dimensional magnetic resonance imaging data set resulting from a magnetic resonance imaging acquisition of an imaging volume for the same joint of the same patient, and comparing surface data resulting from the step of segmenting with volumetric data resulting from the second data set.
In preferred embodiments, the step of comparing can be part of a step of segmenting the same boundary between two anatomical features of the patient based on the second magnetic resonance imaging data set. The step of comparing can be part of a second step of spatially registering the boundary between the anatomical features segmented in the first data set with the second data set.
In another general aspect, the invention features a magnetic resonance imaging system that includes means for obtaining a first three-dimensional magnetic resonance imaging data set resulting from magnetic resonance imaging acquisition from a joint of a patient, means for segmenting a boundary between two anatomical features of the joint of the patient based on the first magnetic resonance imaging data set, means for obtaining a second three-dimensional magnetic resonance imaging data set resulting from a magnetic resonance imaging acquisition from the same joint of the same patient, and means for comparing surface data resulting from the step of segmenting with volumetric data resulting from the second data set.
Systems and methods according to the invention are advantageous in that they can allow precise quantitative tracking of the progression of diseases, such as rheumatic diseases affecting the cartilage. Such precise quantitative tracking can allow for accurate evaluation of the effects of pharmaceutical agents on these diseases in clinical trials. It may also allow physicians to accurately determine how and when to treat individual patients.
Systems according to the invention may also provide more insight into disease progression. Because they allow physicians to view the effect of disease on different joint structures, systems according to the invention may permit physicians to gain a more detailed insight into the studied disease for a patient or group of patients. This may result in more finely targeted treatment research, or more effectively administered treatment delivery.
The benefits described above can be provided in a highly efficient manner. Because many aspects of systems and methods according to the invention are extensively automated, little operator intervention is necessary. And because such systems and methods are highly sensitive, relatively short follow-up periods may be achievable. These efficiencies can have a significant impact on the cost of large-scale clinical studies, where many patients must be carefully evaluated. These cost savings may result in the evaluation of a larger number of potential treatments.